The time for an HIV vaccine is now.
HIV vaccines were not part of the main stage at the Durban Aids Conference held in 2000. Our knowledge and experience in HIV vaccine development were rudimentary at this time; our journey to understanding the complexity of designing immunogens to elicit effective immune responses was just beginning. But HIV vaccines are a now pivotal part of the prevention research agenda: there is scientific optimism about the ability to develop an effective vaccine and South Africa is now a central point in this research. The intervening 16 years between the Durban conferences has brought a series of hard-won understandings about how HIV works in orchestrating its transmission from person to person and between communities.
Our past approaches to vaccine development have largely been ineffective because the virus’s exterior coating, what we call its envelope structure, has areas of immune dampening. In these areas, immune decoys are set up and evolve so cleverly that the initial, critical antibodies that are made to fight HIV appear so similar to parts of ourselves that the virus can hijack the mechanism that our immune system employs to prevent rejecting our own bodies.
The virus also “plays” with the other arm of the immune system: our T-cell function. Again, it causes our immune system to recognise virus-contaminated cells later than normal and often disrupts the ability of immune cells to engulf or damage virus-infected cells.
We therefore have had to learn a new “rule book” for HIV vaccine development. This has taken time, resources, collaboration and support from communities interested in vaccine development. There are no validated animal models for an HIV vaccine and hence all this knowledge needs to be collected in humans willing to enter experimental HIV vaccine studies. Fortunately, the global community has been embracing these ideals. The countries playing the leading roles in these endeavours are South Africa, the United States and Thailand, where the vast majority of HIV vaccine trials have been conducted since Durban 2000.
The only HIV vaccine to show modest efficacy was the RV144 trial, conducted in more than 16 000 heterosexual adults in Thailand between 2003 and 2009. The RV144 trial proved that a vaccine approach could reduce HIV acquisition, and this was a major lift for the field. The vaccine tested combined a prime vaccine called ALVAC‐HIV with a boost of another vaccine, the AIDSVAX gp120. It prevented HIV infection in about 30% of trial participants. These findings were a surprise to many and a reminder of the importance of clinical trials in humans.
But this regimen induced no neutralising antibody responses — a neutralising antibody is an antibody that defends a cell from an antigen or infectious body by neutralising any effect it has biologically. Instead, protection appeared to be correlated with binding antibodies, robust CD4 T-cell responses and other antiviral activities.
Testing and trials will continue in the search for an HIV vaccine
In 2010, shortly after RV144, a public-private partnership known as the P5 Partnership convened to take the findings from the Thai study and adapt the regimen for testing in sub-Saharan Africa. In order to better match the “Thai vaccine” to the sub-Saharan population, P5 redesigned the ALVAC vector with a Clade C and a new Clade C protein boost. Clade C is the most common clade of HIV in sub-Saharan Africa. This vaccine has been tested in South Africa in the HVTN 100 trial, and the results of this trial will be presented at this year’s conference.
These results show that this regimen appears to have improved immune responses to those seen in the RV144 trial, and hence passed the bar established by the scientific community to move ahead. Based on the promising immunogenicity (the ability of a substance to provoke an immune response in the body) found in this study, a large-scale efficacy study is scheduled to kick off in South Africa towards the end of 2016.
This year has also seen the initiation of two proof-of-concept studies evaluating the role of the potent neutralising antibody VRC01, discovered in an elite viral controller. VRC01 demonstrated protection in animal studies. These studies will investigate the effectiveness of VRC01 and the level of neutralising activity required in reducing HIV acquisition in homosexual men in the Americas and heterosexual women in sub-Saharan Africa, creating new methods of protection.
Durban 2000 marked the beginning of the era of effective antiretroviral therapy in resource-constrained settings, with life-saving results. But despite this progress, millions of new HIV infections continue to occur each year. The world desperately needs a safe and effective preventive HIV vaccine. The Durban 2016 conference signals the beginning of research into a new generation of HIV vaccines. We hope that one day we will look back at Durban 2016 as a crucial moment in time for HIV vaccine development and the realisation of an Aids-free world.
Professor Glenda Gray is president of the South African Medical Research Council. Scott Hammer is professor of epidemiology at Columbia University’s Mailman School of Public Health. Professor Larry Corey is emeritus director of the Fred Hutchinson Cancer Research Center in Seattle.
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